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Pelvic organ prolapse (POP) is a group of diseases caused by extracellular matrix (ECM) degradation in pelvic supportive tissues. Cysteine and serine rich nuclear protein 1 (CSRNP1) is involved in cell proliferation and survival regulation, and reportedly facilitates collagen breakdown in human chondrocytes. The present study aimed to probe the effect of CSRNP1 on collagen metabolism in human-derived vaginal fibroblasts. High expression of CSRNP1 was found in POP patient-derived vaginal fibroblasts in comparison to normal-derived vaginal fibroblasts. Following functional experiments revealed that CSRNP1 overexpression led to proliferation inhibition, apoptosis and collagen degradation in normal vaginal fibroblasts. In line with this, silencing of CSRNP1 inhibited hydrogen peroxide (H2O2)-triggered apoptosis, ROS generation and collagen loss in normal vaginal fibroblasts. Silencing of CSRNP1 also reduced the expression of cell senescence markers p21 and γ-H2Ax (the histone H2Ax phosphorylated at Ser139), as well as curbed collagen breakdown in normal vaginal fibroblasts caused by a DNA damage agent etoposide. Transcriptomic analysis of vaginal fibroblasts showed that differentially expressed genes affected by CSRNP1 overexpression were mainly enriched in the Wnt signaling pathway. Treatment with a Wnt pathway inhibitor DKK1 blocked CSRNP1 knockdown-caused collagen deposition. Mechanistically, CSRNP1 was identified to be a target of Snail family transcriptional repressor 2 (SNAI2). Forced expression of CSRNP1 reversed the anti-apoptotic, anti-senescent and anti-collagen loss effects of SNAI2 in normal vaginal fibroblasts exposed to H2O2 or etoposide. Our study indicates that the SNAI2/CSRNP1 axis may be a key driver in POP progression, which provides a potential therapeutic strategy for POP.
Assuntos
Apoptose , Senescência Celular , Colágeno , Dano ao DNA , Fibroblastos , Estresse Oxidativo , Vagina , Feminino , Humanos , Apoptose/genética , Proliferação de Células , Células Cultivadas , Senescência Celular/genética , Colágeno/metabolismo , Fibroblastos/metabolismo , Inativação Gênica , Peróxido de Hidrogênio/farmacologia , Prolapso de Órgão Pélvico/metabolismo , Prolapso de Órgão Pélvico/genética , Prolapso de Órgão Pélvico/patologia , Fatores de Transcrição da Família Snail/metabolismo , Fatores de Transcrição da Família Snail/genética , Vagina/metabolismo , Vagina/citologia , Vagina/patologiaRESUMO
Antimicrobial peptides (AMPs) are usually small and cationic biomolecules with broad-spectrum antimicrobial activities against pathogens. Purifying them from complex samples is essential to study their physiochemical properties. In this work, free-flow zone electrophoresis (FFZE) was utilized to purify AMPs from yeast fermentation broth. Meanwhile, gel filtration chromatography (GFC) was conducted for comparison. The separation efficiency was evaluated by SDS-PAGE analysis of the fractions from both methods. Our results demonstrated as follows: (i) FFZE had more than 30-fold higher processing capacity as compared with GFC; (ii) FFZE could achieve 87% purity and 89% recovery rate while in GFC these parameters were about 93 and 82%, respectively; (iii) the former had â¼2-fold dilution but the latter had â¼13-fold dilution. Furthermore, Tricine-SDS-PAGE, Native-PAGE, and gel IEF were carried out to characterize the purified AMPs. We found that two peptides existed as a pair with the molecular mass of â¼5.5 and 7.0 kDa, while the same pI 7.8. These two peptides were proved to have the antimicrobial activity through the standardized agar diffusion method. Therefore, FFZE could be used to continuously purify AMPs with high bioactivity, which will lead to its wide application in the clinical and pharmaceutical fields.
Assuntos
Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Cromatografia em Gel/métodos , Eletroforese/métodos , Peptídeos Catiônicos Antimicrobianos/análise , Peptídeos Catiônicos Antimicrobianos/química , Eletroforese em Gel de PoliacrilamidaRESUMO
INTRODUCTION AND HYPOTHESIS: This study aims to investigate clinical therapeutic measures for women with urinary incontinence (UI) complicated with diabetes mellitus (DM). METHODS: We performed a retrospective cohort study, including 462 female patients with UI complicated with DM (group A) and 901 patients with UI without DM (group B). Both A and B groups were divided into three subgroups according to their UI types (pure stress UI, mixed UI dominated by urge UI, and by overactive bladder syndrome) and received corresponding treatments. The subjective and objective effective rates were analyzed statistically. RESULTS: The overall subjective effective rates were 62.99% and 85.23% and the overall objective effective rates were 67.53% and 87.24% for groups A and groups B, respectively; the subjective and objective effective rates were 73.68% and 89.47% for group A1 (patients with pure stress UI in group A). There was no statistical difference in group A1 between subjective and objective effective rates. CONCLUSION: Unsatisfactory clinical therapeutic efficacy was observed in women with UI complicated with DM; surgical operation should be deliberated cautiously for women with SUI complicated with DM.
Assuntos
Complicações do Diabetes/complicações , Intervenção Médica Precoce/métodos , Incontinência Urinária por Estresse/terapia , Incontinência Urinária de Urgência/terapia , Incontinência Urinária/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Comportamental , Estudos de Coortes , Tratamento Farmacológico , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Bexiga Urinária Hiperativa/etiologia , Bexiga Urinária Hiperativa/terapia , Incontinência Urinária/etiologia , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária de Urgência/etiologiaRESUMO
Introduction: Post-radical-hysterectomy (RH) patients suffer from a series of problems resulting from neurovascular injury, such as bladder dysfunction, which reduce their quality of life. We have designed this study to evaluate the efficacy of transcutaneous electrical stimulation (TENS) on patient rehabilitation after RH for early cervical cancer. Materials and methods: A total of 97 patients were enrolled in a randomized-controlled trial (from January 2015 to December 2019) involving 7 medical centers nationwide. Patients were assigned to either the intervention group (n = 46), or the control group (n = 51). TENS was given to patients in the intervention group from the 7th day after surgery for a total of 14-21 days. The control group received no TENS. Primary outcomes were measured for residual urine volume and recovery of urination function. Secondary outcomes were measures for urodynamics (UDS), pelvic floor electromyography function examination (PFEmF), and quality of life (QoL). Results: Residual urine volume and improvement in the rate of urination were found to show no significant differences on the 14th, 21st, and 28th days after surgery. The maximum flow rate (Qmax) in the intervention group was significantly higher than that in the control group on the 28th day, but there were no significant differences in average flow rate, voiding time, time to Qmax, muscle fiber strength, muscle fiber fatigue, and the abnormal rate of A3 reflection on the 28th day and the 3rd mo., as well as in the QoL at 3rd mo., 6th mo., and 12th mo. after surgery. Conclusion: Our study showed no sufficient evidence to prove that TENS under the trialed parameters could improve the subject's voiding function, PFEmF, and QOL after RH. This has provided valuable data for rehabilitation after RH. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02492542.
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BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, Pâ<â0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, Pâ<â0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER: NCT03620565, https://register.clinicaltrials.gov.
Assuntos
Diafragma da Pelve , Prolapso de Órgão Pélvico , China , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Diafragma da Pelve/cirurgia , Prolapso de Órgão Pélvico/cirurgia , Telas Cirúrgicas/efeitos adversos , Resultado do Tratamento , VaginaRESUMO
PURPOSE: To investigate the effect of total pelvic floor reconstruction with a six-arm mesh in the treatment of pelvic organ prolapse. PATIENTS AND METHODS: This is a retrospective observational cohort study. A total of 368 patients with pelvic organ prolapse underwent pelvic floor reconstruction surgery. Patients were categorized by the type of surgical mesh: 176 patients received a six-arm mesh and 192 patients received an anteroposterior approach mesh. The 1-year effect of the two groups was compared. The Pelvic Floor Distress Inventory Questionnaire (PFDI-20), Colorectal-Anal Distress Inventory (CRADI-8) and the Pelvic Organ Prolapse Quantitation (POP-Q) staging were used for evaluation. The incidence of complications was recorded. A cure standard was registered by a POP-Q score of grade I or below. A P value <0.05 indicates the difference is statistically significant. RESULTS: There was no recurrence documented in the patients; the cure rate was 100% in both groups. After surgery, the length of the vagina in the six-arm mesh group was longer than that of the control group at 6 months and 12 months, respectively (P < 0.05). The six-arm mesh group had lower PFDI-20 and CRADI-8 scores after surgery than those of the control group at 6 and 12 months, respectively (P < 0.05). Pelvic floor and rectal dysfunction symptom improvement were superior in the six-arm mesh group compared with the control group. After surgery, the Female Sexual Function Inventory (FSFI) score of the six-arm mesh group was superior to that of the control group at 6 and 12 months, respectively (P < 0.05). The incidence of complications in the six-arm mesh group was lower than that of the control group (P < 0.05). CONCLUSION: The total pelvic floor reconstruction using six-arm mesh has the same healing rate as anteroposterior approach mesh surgery, and it is better than traditional surgery in improving subjective symptoms and reducing postoperative complications.
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BACKGROUND: Fecal incontinence (FI) has been shown to be a common symptom in Western countries; however, there is few researches focusing on its epidemic condition in Chinese women. We conducted this national population-based epidemiology study to estimate the prevalence and risk factors of FI among adult Chinese women living in urban regions. METHODS: This is a subgroup analysis of a national population-based epidemiology study of FI. Total 28,196 adult women from urban regions of six provinces and municipalities participated in this research from 2014 to 2015. They finished the questionnaire under the direction of trained interviewers. FI was defined as accidental leakage of flatus and/or liquid or solid stool at least once in the past. The FI prevalence trend and risk factors were identified by the Cochran-Armitage test, Chi-square test, and multivariable logistic regression. RESULTS: The prevalence of FI in adult females in urban China was 0.43% (95% confidence interval: 0.35%-0.51%). Among women with FI, 42.96%, 82.96%, and 42.22% reported having leakage of solid, liquid stool, and gas, respectively. The overall FI prevalence and the incidence rate of solid stool/liquid stool/gas leakage increased with age. The mean Wexner score was 4.0% and 12.0% FI patients reported Wexner score ≥9. Body mass index ≥24 kg/m, pelvic organ prolapses, chronic constipation, chronic cough, alcohol consumption, physical diseases including chronic bronchitis and cancer, gynecological diseases like gynecological inflammation are risk factors for FI. Vaginal delivery was the risk factor for FI in females with labor history. CONCLUSIONS: FI was not a common symptom in adult Chinese women living in urban areas and there were some potential modifiable risk factors. TRIAL REGISTRATION: Chinses Clinical Trial Registry: ChiCTR-OCS-14004675; http://www.chictr.org.cn/showproj.aspx?proj=4898.
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Incontinência Fecal/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Incontinência Fecal/etiologia , Feminino , Humanos , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
OBJECTIVE: To explore the expression and significance of ME491/CD(63) and integrin alpha5 protein and mRNA in ovarian cancer. METHODS: The expression levels of ME491/CD(63) and integrin alpha5 proteins and mRNA were evaluated by using RT-PCR and hybridization in situ (HIS) in normal ovarian tissues (G(1)), ovarian benign tumor tissues (G(2)), ovarian borderline tumor tissues (G(3)) and ovarian cancer tissues (G(4)). The expression levels of ME491/CD(63) genes and proteins were analyzed by multivariant analysis and their effects on the invasion and metastases of ovarian cancer were explored and their correlation with age at surgery, metastatic sites, operation fashions, lymph status, operation pathological staging and pathological typing was studied. RESULTS: The results showed the exact biological effects of ME491/CD(63) and integrin alpha5 in ovarian cancer tissues. The tendency of two methods is coincidence on the whole. There was positive expression of ME491/CD(63) and integrin alpha5, and ME491/CD(63) mRNA expression levels were 1.7 +/- 0.3 and 1.5 +/- 0.3, and integrin alpha5 mRNA expression levels were 1.7 +/- 0.3 and 1.5 +/- 0.3 in G(1) and G(2); ME491/CD(63) is 1.1 +/- 0.5, and integrin alpha5 is 1.1 +/- 0.5 in G(3); ME491/CD(63) is 0.6 +/- 0.4, integrin alpha5 is 0.6 +/- 0.4 in G(4); There was no significant relationship between gene expression and age at surgery or clinical-pathological staging (P > 0.05). There was significant difference between G(1), G(2) and G(3) (P < 0.01), while no difference between G(1) and G(2) (P > 0.05). Low expression levels in G(4) (III, IV) were observed. Significant differences were noted between expression levels in G(4) (III, IV) and in G(2), G(3) or G(4) (I, II; P < 0.01). There was significant difference between expression levels in tissues with lymph metastases and tissues without lymph metastases (P < 0.01). CONCLUSIONS: ME491/CD(63) and integrin alpha5 are lowly expressed and negatively correlated with ovarian cancer. Different expression levels exist in tissues of late ovarian cancer, earlier ovarian cancer, benign ovarian tumor and borderline tumor. The changes of two genes are correlated with tumor differentiation degree, but not pathologic typing.
Assuntos
Antígenos CD/biossíntese , Integrina alfa5/biossíntese , Linfonodos/patologia , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Glicoproteínas da Membrana de Plaquetas/biossíntese , Adolescente , Adulto , Idoso , Antígenos CD/genética , Feminino , Humanos , Integrina alfa5/genética , Metástase Linfática , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Glicoproteínas da Membrana de Plaquetas/genética , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tetraspanina 30RESUMO
OBJECTIVE: To investigate correlation between key diameters of pelvic inlet and outlet planes and female pelvic floor dysfunction (FPFD). STUDY DESIGN: Correlation with incidence of FPFD was analyzed by measuring the two diameters of pelvic inlet and outlet planes (i.e. anteroposterior diameter of pelvic inlet and transverse diameter of pelvic outlet) in 298 patients with FPFD and 508 patients in control group taking into account of other relevant factors. RESULTS: The transverse diameter of pelvic outlet was significantly larger in experimental group than in control group (9.55cm vs. 8.50cm, P<0.01); while the difference in anteroposterior diameter of pelvic inlet between the two groups was not statistically significant (11.63cm vs. 11.26cm, P=0.205>0.01); Binary logistic regression analysis indicated that the anteroposterior diameter of pelvic inlet was not correlated with incidence of FPFD, but the transverse diameter of pelvic outlet was one of the influencing factor for FPFD. CONCLUSIONS: The transverse diameter of pelvic outlet is closely correlated with incidence of FPFD and represents one of the risk factors for FPFD; a transverse diameter of pelvic outlet greater than 9.5cm is the threshold for onset of FPFD and can be used as an early predictive index for FPFD.